Department of Physiology and Pharmacology, Universidade Federal do Ceará, CEP: 60430-270, Brazil.
Chem Biol Interact. 2013 Sep 25;205(2):148-56. doi: 10.1016/j.cbi.2013.07.005. Epub 2013 Jul 16.
Our great interest in this work was study the synergism between l-tryptophan and dipyrone or paracetamol as well as the interaction of kynurenic acid (l-tryptophan metabolite) and these analgesics agents utilizing a robust methodology.
We performed the writhing test induced by acetic acid in mice to evaluate the antinociceptive effect of the treatments isolated and combined (p.o. and i.p.). Dose-response curves were constructed and the values of ED50 for treatment alone and combined were statistically compared. In addition, isobolographic analysis was performed and the experimental values were compared with the theoretical values for simple additive effect.
The combined treatment with l-tryptophan and dipyrone or paracetamol reduced significantly the ED50 of these analgesics when compared to the isolated treatments. l-tryptophan alone has no antinociceptive effect. l-Tryptophan increases the central amount of 5-HT and the synergism with dipyrone is antagonized by the 5-HT depletion. The kyna has an antinociceptive dose-related effect and a synergistic interaction with dipyrone and paracetamol verified by isobolographic analyses and confirmed by experimental values of ED50 of combined treatments were statistically lower than theoretical calculated values for simple additive effect. Melatonin antagonist receptor attenuates the antinociceptive synergism between l-tryptophan and dipyrone.
Our results demonstrate that the increased 5-HT amount on the central nervous system is not per se capable to induce antinociception. The l-tryptophan interacts synergistically with dipyrone and paracetamol both orally and by i.p. route. This effect is dependent on the biotransformation of l-tryptophan to 5-HT and involves kynurenic acid and melatonin receptors.
我们对这项工作非常感兴趣，旨在研究 l-色氨酸与二吡咯酮或扑热息痛的协同作用，以及犬尿酸（l-色氨酸代谢物）与这些镇痛剂的相互作用，利用一种强大的方法。
我们在小鼠中进行了醋酸诱发的扭体试验，以评估单独和联合（po 和 ip）治疗的镇痛效果。构建剂量-反应曲线，并对单独和联合治疗的 ED50 值进行统计学比较。此外，进行了等比分析，并将实验值与简单相加效应的理论值进行比较。
与单独治疗相比，l-色氨酸与二吡咯酮或扑热息痛联合治疗显著降低了这些镇痛药的 ED50。l-色氨酸单独使用没有镇痛作用。l-色氨酸增加了中枢 5-HT 的含量，与二吡咯酮的协同作用被 5-HT 耗竭所拮抗。犬尿酸具有剂量相关的镇痛作用，并与二吡咯酮和扑热息痛具有协同相互作用，通过等比分析得到验证，并且联合治疗的 ED50 的实验值低于简单相加效应的理论计算值，具有统计学意义。褪黑素受体拮抗剂可减弱 l-色氨酸与二吡咯酮的镇痛协同作用。
我们的结果表明，中枢神经系统中 5-HT 含量的增加本身并不能引起镇痛作用。l-色氨酸与二吡咯酮和扑热息痛在口服和 ip 途径均具有协同作用。这种作用依赖于 l-色氨酸向 5-HT 的生物转化，并涉及犬尿酸和褪黑素受体。
